title: Brucella abortus induces collagen deposition and MMP-9 down-modulation in hepatic stellate cells via TGF-β1 production.
abstract: In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis. Herein, we examine some potential mechanisms of liver damage in brucellosis. We demonstrate that Brucella abortus infection inhibits matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic stellate cells (LX-2). These phenomena depend on transforming growth factor-β1 induction. In contrast, supernatants from B. abortus-infected hepatocytes and monocytes induce MMP-9 secretion and inhibit collagen deposition in hepatic stellate cells. Yet, if LX-2 cells are infected with B. abortus, the capacity of supernatants from B. abortus-infected hepatocytes and monocytes to induce MMP-9 secretion and inhibit collagen deposition is abrogated. These results indicate that depending on the balance between interacting cells and cytokines of the surrounding milieu, the response of LX-2 cells could be turned into an inflammatory or fibrogenic phenotype. Livers from mice infected with B. abortus displayed a fibrogenic phenotype with patches of collagen deposition and transforming growth factor-β1 induction. This study provides potential mechanisms of liver immune response induced by B. abortus-infected hepatic stellate cells. In addition, these results demonstrate that the cross talk of these cells with hepatocytes and macrophages implements a series of interactions that may contribute to explaining some of mechanisms of liver damage observed in human brucellosis.
authors.affiliation: Institute of Immunology, Genetics, and Metabolism, Jose de San Martin Clinical Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Arriola Benitez
authors.affiliation: Institute of Immunology, Genetics, and Metabolism, Jose de San Martin Clinical Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Scian
authors.affiliation: Biotechnology Research Institute, Technology Institute of Chascomús, National University of San Martin National Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Comerci
authors.affiliation: Biotechnology Research Institute, Technology Institute of Chascomús, National University of San Martin National Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Diego Rey
authors.initials: DR
authors.lastname: Serantes
authors.affiliation: Institute of Experimental Medicine, National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vanzulli
authors.affiliation: Institute for the Study of Humoral Immunity, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina; Laboratory of Immune System Research, Faculty of Exact Sciences, National University of La Plata, La Plata, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Fossati
authors.affiliation: Institute of Immunology, Genetics, and Metabolism, Jose de San Martin Clinical Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.affiliation: Institute of Immunology, Genetics, and Metabolism, Jose de San Martin Clinical Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. Electronic address: mdelpino@ffyb.uba.ar.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Delpino
mesh_terms: D000818:Animals; D002003:Brucella abortus; D002006:Brucellosis / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D003094:Collagen; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse